Abstract
Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.
Highlights
Herpetic Keratitis (HK) induced by herpes simplex virus type 1 (HSV-1) ocular infection is a leading cause of infectious blindness
To confirm that the VC2 vaccine strain that contains the glycoprotein K (gK) and the UL20 amino terminal deletions cannot infect neuronal endings, travel to the trigeminal ganglion (TG) and establish latency, mouse corneas of naïve mice were infected with 106 PFU per eye after mild-scarification with either the HSV-1(F) parental wild-type virus or the VC2 vaccine strain
We reported that VC2 intramuscular vaccination of mice generates robust protection against lethal ocular HSV-1 (McKrae) challenge [18]
Summary
Herpetic Keratitis (HK) induced by herpes simplex virus type 1 (HSV-1) ocular infection is a leading cause of infectious blindness. The use of animal models such as mice and rabbits is wellestablished in ocular HSV-1 research [6]. Data from these animal models suggest that after initial reactivation from the TG, the virus travels to the ocular surface in an anterograde manner [8, 9]. It has been suggested that vaccine-induced immunity can reduce HSV-1 induced HK in animal models [11,12,13,14,15,16,17]. We reported that intramuscular immunization (IM) with the live-attenuated HSV-1 vaccine (VC2) confers complete protection against a lethal HSV-1 challenge and ocular immunopathogenesis [18,19,20]
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